REFILE-Obesity, metabolic syndrome linked with cancer mortality

Last Updated: 2016-09-12

(Corrects author affiliation in paragraph 2.)

By Will Boggs MD

NEW YORK (Reuters Health) - Two new studies suggest that obesity and metabolic syndrome can influence survival with early-stage colorectal cancer or metastatic kidney cancer.

"Considering a patient's metabolic health and body composition adds additional prognostic information for clinicians to consider," Dr. Elizabeth M. Cespedes Feliciano, postdoctoral fellow at the Kaiser Permanente Division of Research in Oakland, California, told Reuters Health by email. "Metabolic dysfunction identifies a group of obese patients who are at high risk and should be monitored closely. Further, not just body mass index and body weight, but also body composition and muscularity should be considered when guiding patients and assessing their risk level."

Previous reports investigating the relationship between overweight/obesity and colorectal cancer (CRC) have yielded inconsistent results. Emerging evidence suggests that metabolic syndrome reduces cancer survival, but no study has examined metabolic syndrome in combination with obesity and its possible association with CRC survival.

Dr. Cespedes Feliciano and colleagues studied 2446 patients with early-stage CRC, stratifying them according to presence/absence of obesity (BMI at least 30 kg/m2) and presence/absence of metabolic syndrome, yielding four groups.

Compared with metabolically healthy nonobese patients, obese patients with metabolic syndrome had 23% higher risk of overall mortality and 24% higher risk of CRC-related mortality, according to the September 6th Journal of Clinical Oncology online report.

These associations were even stronger after adjustment for muscle mass.

"While patients with obesity have more fat than normal-weight patients, they also often have more muscle, and muscularity is protective: lean body mass is important to consider and controlling for it was a novel feature of our study," Dr. Cespedes Feliciano explained. "Fat - in particular, visceral fat, which is strongly associated with metabolic dysfunction, insulin resistance, and inflammation - may be harmful. When we examine obesity and metabolic dysfunction controlling for muscularity, we see more clearly the harms of excess adiposity."

There was a trend toward worse survival among nonobese patients with metabolic syndrome and metabolically healthy obese patients, but these fell short of statistical significance.

Overall and CRC-related survival decreased with the presence of additional metabolic risk factors independent of BMI category at diagnosis.

"Whether optimizing clinical management of metabolic syndrome in newly diagnosed colorectal cancer patients leads to improved survival will be an important area for future research," Dr. Cespedes Feliciano said.

"We do not yet fully understand the mechanisms through which obesity might influence survival after a colorectal cancer, but one hypothesized pathway is through metabolic dysfunction and its hallmarks: insulin resistance and systemic inflammation," she added.

Dr. Daniel Trabulo from Hospital de Sao Bernardo, Centro Hospitalar de Setubal in Portugal, who recently reported an association between metabolic syndrome and colorectal neoplasms, told Reuters Health by email, "Patients with metabolic syndrome have an increased risk of adenomas (and especially multiple adenomas) and colorectal cancer. For this reason, physicians should insist on education, motivation, and promotion of healthy lifestyles, particularly on prevention and early treatment of diabetes, obesity, and dyslipidemia, to fight the battle against this syndrome which is now a pandemic disease."

"Recommendations for colorectal cancer screening in patients with metabolic syndrome may need to be different from the average risk population; this is based on the heads-up data concerning the relationship between metabolic syndrome and colorectal neoplasms," Dr. Trabulo said. "However, there is not enough information to justify colorectal cancer screening before the recommended age in this particular group of patients."

In the second study, Dr. Toni K. Choueiri from Dana-Farber Cancer Institute and Brigham and Women's Hospital, both in Boston, and colleagues investigated the association of BMI with treatment outcomes in two cohorts of patients with metastatic renal cell carcinoma (RCC).

In contrast to the results in patients with CRC, high BMI in patients with metastatic RCC was associated with significantly better overall survival, particularly in the intermediate and poor risk groups of patients.

High BMI was associated with lower expression of the fatty acid synthase gene (FASN), and high FASN expression was associated with worse overall survival. FASN positivity was also more common in the poor and intermediate risk groups.

"FASN is a key enzyme in cells' production of fatty acids, and overexpression of FASN has previously been found in many types of cancer," Dr. Choueiri explained in an email. "FASN acts as a metabolic oncogene. FASN has been associated with poor prognosis in several types of cancer, including kidney cancer."

"Since FASN expression was downregulated in overweight and obese kidney cancer patients, that could explain why these individuals fared better than those who were of normal weight and had increased FASN gene expression," she said. "This may provide a rationale for experiments aimed at inhibiting FASN expression in kidney cancer patients in an effort to improve outcomes. FASN inhibitors have been in development for several years and are considered a promising approach to cancer treatment."

SOURCES: http://bit.ly/2c1Sc0H and http://bit.ly/2ccTsLl

J Clin Oncol 2016.